This study was conducted to investigate the effects of nimesulide in platelet aggregation. It shows that nimesulide (1-100 μ M) inhibited platelets aggregation induced by adrenaline, (20-200 μ M). It also inhibed thromboxane A2 (TXA2) formation by platelets at low concentration (IC50; 1 μ M). However, much lower concentrations of nimesulide (0.01-0.1 μ M) potentiated the aggregatory response of subthreshold concentrations of adrenaline (0.2-2 μ M). Such an effect was blocked by Ca2+-channel blockers, verapamil and diltiazem (IC50: 7 and 46 μ M, respectively), nitric oxide donor, SNAP (IC50: 2 μ M) and cinchonine (10 nM) but not by genistein (up to 10 μ M). These results are indicative of the concentration-dependent dual effects of nimesulide on human platelet aggregation. The synergistic effect of low doses of nimesulide and adrenaline seems to be mediated through inhibition of multiple signaling pathways.
S.A. Saeed , H. Rasheed , T.M. Ali , Y. Qazi , S. Kabraji , L. Paul , R. Khan , F.A. Hussain and S. Ahmad , 2004. Mechanism of Inhibitory Action of Cyclooxygenase-2 Inhibitors in Human Platelets. Journal of Biological Sciences, 4: 515-520.